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Symptoms of diabetes mellitus

• Basic– Thirst– Polyuria– Weight loss– Fatigue

• Other– Muscle cramps– Obstipation– Blurred vision– Fungal and bacterial

infections

• If you do not begin insulin therapy immediately– nausea, vomitus – abdominal pain – dehydration– Kussmaul breathing – (deep, acetone smell)– ketones in blood,– urine, acidosis

COMA DIABETICUM

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Symptoms of diabetes mellitus

NOTHING

Type 2 for long time (months, years)

Hypertension

Myocardial infarction, stroke with very bad prognosis

Microangiopathic complications (amputation)

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Symptoms of diabetes mellitus

NOTHING

Gestational diabetes mellitus

Screening!

Harmful both for baby and mother

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Symptoms of diabetes mellitus

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Diagnostic criteria of DM• Symptoms of DM and 1 abnormal blood

glucose* value– fasting 7,0 mmol/l– 2h after 75 g glucose or casual 11,1

• No symptoms present– two abnormal BG values on 2 days (as above)

• Not a perfect algorhythm– Uncertainity of BG assays !!!

*Only on laboratory analyzers, from venous plasma; uncertainity 0,5 mmol/l

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Definition of diabetes mellitus

Diabetes mellitus is a group of metabolic diseases characterized by hyperglycemia

resulting from defects in insulin secretion, insulin action, or both.

The chronic hyperglycemia of diabetes is associated with long-term damage, dysfunction, and failure of various organs, especially the eyes, kidneys,

nerves, heart, and blood vessels.

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Two types of diabetes

AGE

SEX

32

m

52

f

9

f

28

m

42

m

35

f

47

f

53

f

46

f

57

m

WEIGHT 46 56 25 41 54 79 69 75 85 83

G/ blood 23,9 21,2 22,5 14,9 17,7 16,2 21,2 17,3 17,3 12,9

G/ urine +++ +++ +++ +++ +++ +++ +++ +++ +++ +++

ketones +++ + +++ + ++ neg neg neg neg neg

insulin 0 0 0 0 0 0,26 0,29 0,02 0,24 0,20

Bornstein & Lawrence, 1951

??

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Classification of diabetic syndromes

Type 1 diabetes mellitus (10 %)autoimmune and idiopathic

IDDM, juvenile diabetes

Type 2 diabetes mellitus (90 %) NIDDM, adult type

Other types of diabetes mellitus (rare, long list) Gestational diabetes mellitus (temporary dg.)

And where is LADA and MODY ?impaired glucose toleranceand impaired fasting glucoseare RISK FACTORS

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Classification of diabetic syndromes

Type 1 diabetes mellitus (10 % ?) Type 2 diabetes mellitus (90 %? ) Other types of diabetes mellitus (rare?, long list) Gestational diabetes mellitus (temporary dg.)

LADA = late autoimmune diabetes of adults

Slow type 1, not very rare, transition between type 1 and 2?

Type 1 and 2 are only endpoints of a scale?

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Classification of diabetic syndromes Type 1 diabetes mellitus (10 % ?) Type 2 diabetes mellitus (90 %? ) Other types of diabetes mellitus (rare?, long list) Gestational diabetes mellitus (temporary dg.)

MODY = maturity onset diabetes of the young

Monogenic forms of diabetes (1 – 7, mostly AD heredity)

Previously classified as T1DM OR T2DM

Not very rare 1,5 – 2 % of patients

Good lessons for genes of T2DM

And also MITOCHODRIAL DIABETES

TRANSIENT NEONATAL DIABETES

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Definition of diabetes mellitus

Diabetes mellitus is a group of metabolic diseases characterized by hyperglycemia

resulting from defects in insulin secretion insulin action, or both.

The chronic hyperglycemia of diabetes is associated with long-term damage, dysfunction, and failure of various organs, especially the eyes, kidneys,

nerves, heart, and blood vessels.

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Type 1 diabetes – geographic differences, Type 1 diabetes – geographic differences, hot spots and genetic backgroundhot spots and genetic background

Peak: 10-25 yearsIn any ageLast years – very low ageINCIDENCE = cases/100 000/y• Finnland: 41• USA 15• Germany 7• Greece: 5• Mexico, Japan, Cuba < 5• Sardinia 32 (hot spot)

HLA haplotypes and DM 1

DR3/DR3 5.0

DR4/DR4 6.8

DR3/DR4 14.3

DR3/X 0.7

DR4/X 1.0

X/X 0.04

95% of DM 1 patients posses DR3 or 4 but these haplotypes are common in population!

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Genes of MHC (HLA) system

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Groove for peptides on MHCglycoproteins

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Interaction between T lymphocyte, and antigen presenting cells

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Etiology of type 1 diabetes• The genetic background is related to the immune system

(HLA glycoproteins are parts of antigen presenting cells*) (Susceptibility to autoimmune destruction of cells)

• External trigger – viral infections, cow milk protein (Islet cell antibodies, Insulin autoantibodies, antiGAD

present already before the manifestation)

• Long process, when the number of cells is < 5-10 % acute manifestation of symptoms in some days – weeks

Without insulin death in coma

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Etiology of type 1 diabetes• The genetic background is related to the immune system

(HLA glycoproteins are parts of antigen presenting cells*) (Susceptibility to autoimmune destruction of cells)• External trigger – viral infections, cow milk proteinThe role of other genesThe actual constellation of immune system –

nonderstructive or destructive insulitis (Islet cell antibodies, Insulin autoantibodies, antiGAD

present already before the manifestation)• Long process, when the number of cells is < 5-10 % acute

manifestation of symptoms in some days – weeks Without insulin death in coma

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Definition of diabetes mellitus

Diabetes mellitus is a group of metabolic diseases characterized by hyperglycemia

resulting from defects in insulin secretion, insulin action, or both.

The chronic hyperglycemia of diabetes is associated with long-term damage, dysfunction, and failure of various organs, especially the eyes, kidneys,

nerves, heart, and blood vessels.

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Etiology of type 2 diabetes mellitusEtiology of type 2 diabetes mellitus

• Heterogenous group of patients (heterogenous disease !)

• Mostly obese adults, family background• Long period without complains, no ketosis• Often hypertension, CHD• At the beginning hyperinsulinemic (insulin

resistant), later the secretion of insulin decreases – T2DM is a progressive disease

• Diabetes is only the end of the story!

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GLUT4

IR

INSULIN

glucose

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GLUT4

IR

INSULIN

glucose

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„disorder of secretion and disturbance of function“

performance of B cells

burden - obesity

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Secretion disorder is the first

Genes regulating the intrauterine development of Langerhans islets

Lessons from an extreme rare condition transient neonatal diabetes

Small babies and DM2

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Different performance

Different burden

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Everything is more complicated

• Increase of BG – secretion of insulin• No insulin (T1DM)• Disturbed function of signal pathway

(T2DM)• But our diet does not contain glucose!• ENTEROINSULAR AXIS! – INCRETINS• Glucagon like protein I and its decreased

activity in T2DM?

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TYPE 2 DIABETES IS THETYPE 2 DIABETES IS THETIP OF THE ICEBERGTIP OF THE ICEBERG

05

101520253055 % TYPE 2 DIABETES MELLITUS % TYPE 2 DIABETES MELLITUS

often undiagnosedoften undiagnosedusual diagnosed too late usual diagnosed too late microvascular complications presentmicrovascular complications presentatherosclerosis acceleratedatherosclerosis accelerated

12 % IMPAIRED GLUCOSE TOLERANCE12 % IMPAIRED GLUCOSE TOLERANCE**atherosclerosis acceleratedatherosclerosis accelerated

cca 25 % INSULIN HYPERSECRETIONcca 25 % INSULIN HYPERSECRETION(INSULIN RESISTANCE, (INSULIN RESISTANCE, METABOLIC METABOLIC SYNDROME)SYNDROME)

impaired sympathetic regulation ?impaired sympathetic regulation ?obesity, hypertension, impaired lipid statusobesity, hypertension, impaired lipid statusatherosclerosis acceleratedatherosclerosis accelerated

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TYPE 2 DIABETES IS THETYPE 2 DIABETES IS THETIP OF THE ICEBERGTIP OF THE ICEBERG

05

101520253055 % TYPE 2 DIABETES MELLITUS % TYPE 2 DIABETES MELLITUS

12 % IMPAIRED GLUCOSE TOLERANCE12 % IMPAIRED GLUCOSE TOLERANCE**cca 25 % INSULIN HYPERSECRETIONcca 25 % INSULIN HYPERSECRETION

WHY ???WHY ???NondiagnosedNondiagnosedLate diagnosedLate diagnosedObesityObesityAging of the whole populationAging of the whole population

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CVD & DM 2 PREVENTION, 2CVD & DM 2 PREVENTION, 211stst CENTURYCENTURY

NUTRITION energycomposition , micronutrients

SMOKING & ALCOHOL HUNTING & GATHERING (PHYSICAL ACTIVITY)HEALTH AWARENESS

weight control blood lipids, glucose blood pressure inherited and acquired health risks

55% S, 55% S, 30% F30% F, 15% P, 15% P